TABLE 1: Considerations for epidemiologic credibility in the assessment of cumulative evidence on genetic associations
(a) For example, if the association pertains to the presence of homozygosity for a common variant and if the frequency of homozygosity is 3%, then category A amount of evidence requires over 30,000 subjects and category B between 3,000 and 30,000. The sample size refers to subjects when genotype contrasts are used, and to alleles when alleles are contrasted.
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TABLE 2: Power calculations for associations with nminor = 1000 for various ORs and various frequencies of the minor genetic group (f minor)6
(a) All calculations assume the same number of cases and controls; results are relatively robust to modest deviations in the allocation ratio. The minor genetic group is the smallest of the two groups contrasted and may have been selected based on genotype or allele considerations.
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TABLE 3: Typical biases and their typical impact on associations depending on the status of the evidence
Category decreases from A to B, if the ‘Unknown’ are considered to be a major issue for the appraisal of the evidence. Any ‘Possible/high’ item confers category C status. ‘Possible’ (selective reporting biases for non-consortium/prospective meta-analysis) does not necessarily decrease the category grade (from A to C); this may need to be appraised separately in each field and may be facilitated by using tests for selective reporting biases (tests for small-study effects and excess of significant studies), although probably no test has high sensitivity and specificity for such biases. Clear demonstrable biases in other aspects of the design, conduct and analysis of the evidence (besides the four aspects considered in this table) also result in shift to category C for protection from bias.
(a) Including groups of clearly different descent without consideration to this diversity. (b) The ethnic population structure may need to be considered also on a case-by-case basis.
OR, odds ratio; PCA, principal component analysis.
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TABLE 4: Variation in the volume of human genome epidemiology evidence for selected diseases, 2001–66
(a) Data from the HuGE published literature database run November 27, 2006; does not include data on genome-wide associations that started appearing for some of these phenotypes (e.g. type 2 diabetes or breast cancer) in early 2007.
(b) Includes studies on bone mineral density.
(c) Includes studies on gestational age.
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TABLE 5: Considerations for assessment of clinical and public health relevance and importance of genetic associations
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